Platyconic Acid A, Platycodi Radix-Derived Saponin, Suppresses TGF-β1-Induced Activation of Hepatic Stellate Cells via Blocking SMAD and Activating the PPARγ Signaling Pathway

Choi, Jae Ho; Kim, Seul Mi; Lee, Gi Ho; Jin, Sun Woo; Lee, Hyun Sun; Chung, Young Chul; Jeong, Hye Gwang

doi:10.3390/cells8121544

Cited by 11 publications

(5 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Results of the present study demonstrated that PA exerted no effect on MRC-5 cell viability at concentrations of 0.5, 1.0 and 2.0 µM. A previous study reported that PA inhibits TGF-β1-induced proliferation of hepatic fibroblasts in a dose-dependent manner (33). The results of the present study demonstrated that TGF-β1 induction significantly increased proliferation of MRC-5 cells; however, PA treatment markedly inhibited the over-proliferation induced by TGF-β1.…”

Section: Discussioncontrasting

confidence: 55%

“…To date, only a small number of drugs have been approved for the treatment of pulmonary fibrosis-associated diseases, such as idiopathic pulmonary fibrosis (IPF), which exhibits a poor prognosis (31). The results of previous studies have demonstrated the role of PG in treatment of pulmonary disease and the anti-liver fibrotic effect of the active component PA (32,33). However, the specific mechanisms involved in the inhibitory effect of PA on pulmonary fibrosis are yet to be fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Platyconic acid A‑induced PPM1A upregulation inhibits the proliferation, inflammation and extracellular matrix deposition of TGF‑β1‑induced lung fibroblasts

Tang

Huang

et al. 2022

Mol Med Rep

View full text Add to dashboard Cite

Platyconic acid A (PA), the active component of Platycodi radix-derived saponin, exerts ameliorating effects on liver fibrosis. Platycodon grandiflorum is used to treat lung disease. Therefore, the present study evaluated the effects of PA on pulmonary fibrosis. Transforming growth factor-β1 (TGF-β1) was used to induce MRC-5 cells to establish an in vitro pulmonary fibrosis model. The viability of MRC-5 cells in the presence or absence of TGF-β1 induction was examined using a Cell Counting Kit-8 assay and the results demonstrated that PA markedly decreased viability of TGF-β1-induced MRC-5 cells in a dose-dependent manner. Wound healing analysis, immunofluorescent staining and western blotting were performed to determine the levels of cell migration and expression of α-smooth muscle actin and extracellular matrix (ECM)-associated proteins. The results of the present study demonstrated that PA significantly suppressed the migration and ECM deposition of TGF-β1-induced MRC-5 cells. Furthermore, results obtained from ELISA and western blotting demonstrated that PA exerted suppressive effects on the inflammation of MRC-5 cells following TGF-β1 stimulation. The mRNA and protein expression levels of protein phosphatase Mg2 + /Mn2 + -dependent 1A (PPM1A) before and after transfection were assessed using reverse transcription-quantitative PCR and western blotting and the results demonstrated that the mRNA and protein expression levels of PPM1A were significantly decreased following transfection with small interfering RNA targeting PPM1A. Moreover, following PPM1A knockdown, PA significantly inhibited the proliferation, migration, inflammation and ECM deposition of TGF-β1-induced MRC-5 cells via activation of the SMAD/ β-catenin signaling pathway. In conclusion, PA activated PPM1A to ameliorate TGF-β1-elicited lung fibroblast injury via modulating SMAD/β-catenin signaling.

show abstract

Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Platyconic acid A‑induced PPM1A upregulation inhibits the proliferation, inflammation and extracellular matrix deposition of TGF‑β1‑induced lung fibroblasts

Tang

Huang

et al. 2022

Mol Med Rep

View full text Add to dashboard Cite

show abstract

“…In this regard, Choi et al showed that PPAR-γ agonists could prevent TGF-β-induced fibrogenesis. They found that PPAR-γ is a new target in the treatment of liver fibrosis and inflammation 70 . A recent study also showed that administration of Lactobacillus amylovorus for 12 weeks reduced the adipocyte and plasma cholesterol levels and also increased the expression of hepatic and adipose PPAR -α 71 .…”

Section: Discussionmentioning

confidence: 99%

The anti-inflammatory effects of Akkermansia muciniphila and its derivates in HFD/CCL4-induced murine model of liver injury

Raftar

Ashrafian

Abdollahiyan

et al. 2022

Sci Rep

View full text Add to dashboard Cite

Inflammation plays a critical role in the promotion of hepatocyte damage and liver fibrosis. In recent years the protective role of Akkermansia muciniphila, a next-generation beneficial microbe, has been suggested for metabolic and inflammatory disorders. In this study, we aimed to evaluate the effects of live and pasteurized A. muciniphila and its extra cellular vesicles (EVs) on inflammatory markers involved in liver fibrosis in a mouse model of a high-fat diet (HFD)/carbon tetrachloride (CCl4)-induced liver injury. Firstly, the responses of hepatic stellate cells (HSCs) to live and pasteurized A. muciniphila and its EVs were examined in the quiescent and LPS-activated LX-2 cells. Next, the anti-inflammatory effects of different forms of A. muciniphila were examined in the mouse model of HFD/CCl4-induced liver injury. The gene expression of various inflammatory markers was evaluated in liver, colon, and white adipose tissues. The cytokine secretion in the liver and white adipose tissues was also measured by ELISA. The results showed that administration of live and pasteurized A. muciniphila and its EVs leads to amelioration in HSCs activation. Based on data obtained from the histopathological analysis, an improvement in gut health was observed through enhancing the epithelium and mucosal layer thickness and strengthening the intestinal integrity in all treatments. Moreover, live A. muciniphila and its EVs had inhibitory effects on liver inflammation and hepatocytes damage. In addition, the tissue cytokine production and inflammatory gene expression levels revealed that live A. muciniphila and its EVs had more pronounced anti-inflammatory effects on liver and adipose tissues. Furthermore, EVs had better effects on the modulation of gene expression related to TLRs, PPARs, and immune response in the liver. In conclusion, the present results showed that oral administration of A. muciniphila and its derivatives for four weeks could enhance the intestinal integrity and anti-inflammatory responses of the colon, adipose, and liver tissues and subsequently prevent liver injury in HFD/CCL4 mice.

show abstract

“…Luciferase reporter assay was performed according to the literature published previously (J. H. Choi et al, 2019). Briefly, HACAT cells were seeded in 96-well plates and were incubated at 37 C overnight.…”

Section: Luciferase Reporter Assaymentioning

confidence: 99%

Kaempferol 3‐O‐gentiobioside, an ALK5 inhibitor, affects the proliferation, migration, and invasion of tumor cells via blockade of the TGF‐β/ALK5/Smad signaling pathway

Zhang

et al. 2021

Phytotherapy Research

View full text Add to dashboard Cite

Overactivation of TGF‐β/ALK5/Smad signaling pathway has been observed in the advanced stage of various human malignancies. As a key component of TGF‐β/ALK5/Smad signaling pathway transduction, TGF‐β type I receptor (also known as ALK5) has emerged as a promising therapeutic target for cancer treatment. In this study, to discover a novel ALK5 inhibitor, a commercial natural products library was screened using docking‐based virtual screening, followed by luciferase reporter assay. A flavonoid glycoside kaempferol 3‐O‐gentiobioside (KPF 3‐O‐G) was identified as a potent ALK5 inhibitor through directly bound to the ATP‐site of ALK5, resulting in the inhibitory effects on phosphorylation and translocation of Smad2 and expression of Smad4. Additionally, we found that KPF 3‐O‐G reduced cell proliferation and inhibited TGF‐β‐induced cell migration and invasion. Moreover, western blotting and immunofluorescent analysis showed that KPF 3‐O‐G significantly reversed the TGF‐β‐induced EMT biomarkers, including upregulation of E‐cadherin and downregulation of N‐cadherin, vimentin, and snail. In vivo study showed that KPF 3‐O‐G administration reduced tumor growth in human ovarian cancer xenograft mouse model, without obvious toxic effect. This study provided novel insight into the anticancer effects of KPF‐3‐O‐G and indicated that KPF‐3‐O‐G might be developed as potential therapeutics for cancer treatment after further validation.

show abstract

Platyconic Acid A, Platycodi Radix-Derived Saponin, Suppresses TGF-β1-Induced Activation of Hepatic Stellate Cells via Blocking SMAD and Activating the PPARγ Signaling Pathway

Cited by 11 publications

References 46 publications

Platyconic acid A‑induced PPM1A upregulation inhibits the proliferation, inflammation and extracellular matrix deposition of TGF‑β1‑induced lung fibroblasts

Platyconic acid A‑induced PPM1A upregulation inhibits the proliferation, inflammation and extracellular matrix deposition of TGF‑β1‑induced lung fibroblasts

The anti-inflammatory effects of Akkermansia muciniphila and its derivates in HFD/CCL4-induced murine model of liver injury

Kaempferol 3‐O‐gentiobioside, an ALK5 inhibitor, affects the proliferation, migration, and invasion of tumor cells via blockade of the TGF‐β/ALK5/Smad signaling pathway

Contact Info

Product

Resources

About